4.1.12 Biophysics

The graduate of the study program Biophysics is proficient in scientific methods of biophysics and can apply them in a creative way to solve a wide range of problems in the field of life sciences (physiology, molecular biology, biochemistry, pharmacology and theoretical medicine, theoretical biology and medicine, immunology, bioinformatics). The graduate is familiar with the methods of state-of-the-art interdisciplinary sciences in the field of biology, nanotechnology, and bioinformatics technologies, as well as their practical application. The graduate scientifically investigates and brings original solutions of problems and has actively acquired research methodology, scientific formulation of the problem, publication of scientific results and their presentation at professional events.

Wolfram syndrome (WS) is a disease caused by a mutation of the WFS1 gene. WFS1 is expressed at high levels in brain and heart, and is localized in the membrane of endoplasmic reticulum (ER) where it modulates the level of calcium and ER stress. Since calcium ions are the principal inductors of myocyte contraction and thus impact cardiac performance, the aim of this work is to reveal the perturbations in calcium homeostasis in WFS1 deficient myocytes and how this affects myocyte shortening and cardiac contractile properties of the WFS1 deficient animals. Modern optogenetic methods, confocal microscopy and advanced image analysis will be applied to determine these parameters.

Calcium ATP-ase of endoplasmic reticulum (SERCA) plays an important role in the calcium homeostasis maintaining as well as in the calcium related signaling. A lot of SERCA structures obtained by crystallographic methods are available in protein databases; however, they provide only data on stabile conformations. Functional changes of SERCA protein are related to the dynamic changes of the structure which will be the object of the study for this thesis. The focus of the work will be a use of docking and molecular dynamics methods for the estimation of structural changes in SERCA induced by endo- and exogenous compounds.

Entrance exams for the academic year 2016/17 were held on 16. 6. 2016 at 10:00 AM. in boardroom of DMCR IMPG SAS

Dissertation topics in the graduate program Biophysics – academic year 2016/2017:

Feedback in calcium signaling during excitation-contraction coupling regulates calcium homeostasis in heart muscle cells, action potential duration, and rate of membrane repolarization, which affects occurence of early afterdepolarizations. The aim of the work is to monitor the impact of local calcium release on the course of inactivation of calcium current, and changes in the molecular complex responsible for feedback that occur during postnatal development and physiological and pathological cardiac hypertrophy. The main methods are patch-clamp in combination with confocal mikroskopy, qPCR and Western blot to determine the expression of the protein and immunofluorescent staining of proteins of the dyadic complex.

Site:

Department of Muscle Cell Research
Institute of Molecular Physiology and Genetics SAS

Topic:

Study of morphological changes in Wolfram syndrome using super-resolution microscopy.

Wolfram syndrome (WS) is a disease caused by a mutation of the WFS1 gene. WFS1 is expressed at high levels in brain and heart, and is localized in the membrane of endoplasmic reticulum (ER) where it modulates the level of calcium and ER stress. In addition, typical WS symptoms are symptoms of mitochondrial disease. The aim of this project is therefore to clarify whether in rats with deletion of the WFS1 gene there are ultrastructural changes in cardiac cells to be detected by super-resolution microscopy as an alternative to electron microscopy techniques.

Site:

Department of Cell Physiology and Genetics
Institute of Molecular Physiology and Genetics SAS

Contraction of cardiac muscle cells occurs after massive release of Ca2+ from the sarcoplasmic reticulum cisternae through activated ryanodine receptors (RYR2s) operating as Ca2+ channels. The main physiological activator of RYR2 channels is cytosolic Ca2+, which binds to the voluminous cytosolic domain. An important role is played by luminal regulation mediated by binding of Ca2+ to the small luminal portion of the RYR2 channel. At present, intensive search for the binding sites on the Ca2+ channel, and the aim of the study will be to acquire new knowledge of the localization of these physiologically important regulatory sites. To achieve the objectives PhD. work electrophysiological experiments at the level of single RYR2 channels will be performed in combination with spectroscopic, biochemical and bioinformatics methods.